Tomassoni Daniele, Amenta Francesco, Di Cesare Mannelli Lorenzo, Ghelardini Carla, Nwankwo Innocent E, Pacini Alessandra, Tayebati Seyed Khosrow
School of Bioscience and Biotechnology, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy.
School of Medicinal and Health Products Sciences, University of Camerino, Via Madonna delle Carceri, 9, 62032 Camerino, Italy.
Biomed Res Int. 2013;2013:985093. doi: 10.1155/2013/985093. Epub 2013 Dec 29.
Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/-)-, (+)-, or (-)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/-)- or (-)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies.
周围神经病变是一类异质性疾病,常表现为痛觉过敏和异常性疼痛。本研究评估了坐骨神经慢性压迫损伤(CCI)是否伴有氧化应激增加和中枢神经系统(CNS)变化,以及这些变化是否对硫辛酸治疗敏感。硫辛酸是一种天然存在的抗氧化剂,有两种旋光异构体(+)-硫辛酸和(-)-硫辛酸以及外消旋形式。它已被提议用于治疗与氧化应激增加相关的疾病。在自发性高血压大鼠(SHR)和正常血压对照群体中制作坐骨神经CCI模型。大鼠未接受治疗或腹腔注射(±)-、(+)-或(-)-硫辛酸14天。评估了运动和感觉脑皮质区域的氧化应激、星形胶质细胞增生、髓鞘状态和神经元损伤。在SHR中观察到氧化应激标志物增加、星形胶质细胞增生和神经元损伤,同时神经丝表达减少。CCI后这种现象更明显。硫辛酸对抗了星形胶质细胞增生和神经元损伤,(+)-硫辛酸比(±)-或(-)-对映体更具活性。这些发现表明硫辛酸对CCI所致的CNS损伤具有神经保护作用,该化合物可能是压迫性神经病变的一种治疗选择。